Early development of the embryo

The aim of this lecture is to consider how the fertilised zygote

begins to develop.

• A great deal of the investigation of embryonic development has been done on animals such as amphibians (frogs and the clawed toad, Xenopus laevis ), echinoderms (sea urchins) and insects (fruit fly, Drosophila melanogaster ) and birds.

• Although many of the concepts and even details of the process are similar in humans and other mammals there are significant differences.

• Frog eggs are about 2000x the size of a mammalian egg and bird’s eggs are even larger. The size is needed in these eggs since the embryo develops externally and independently so the egg must contain all the materials needed for full development of fully formed offspring.

• Mammalian eggs can be much smaller as they develop internally and are nourished via a placenta for most of the developing period.

• However it does mean that mammalian eggs must develop extra structures to allow connection to the maternal uterus which are only used as life support systems and play no part in the structure of the embryo. These extra-embryonic structures are discarded at birth..

• In this course we shall concentrate on the mammalian development with only references and comparisons to development in other species.

Cleavage and morula formation

• The two pronuclei (maternal and paternal) remain separate until the first mitotic division and then the chromosomes merge as they attach to the spindle fibres formed from the sperm centriole.

• This first division is much later in development than equivalent in amphibia and occurs at about 36 hours after fertilisation. The divisions of the early zygote are referred to as cleavage divisions to differentiate them from normal cell division.

• In frogs etc the divisions follow rapidly with nearly complete loss of the G1 and G2 phases and so the daughter cells become progressively smaller as they divide.

• Mammalian development is slower but retains the decrease in size of the cell and the cells are retained within the limits of the zona

pellucida for the first few divisions.

Zona pellucida2 Cell Stage

36 hours

• The cleavage in mammals is even with cells all being equal in size and entirely equivalent (holoblastic cleavage ) unlike frogs and birds ( which show uneven cleavage or meroblastic cleavage).

• It is possible to separate the cells at this stage and each cell is capable of developing into a full normal embryo and this is how identical twins arise (monozygotic twins ie arising from a single zygote).

• In animals up to eight identical octuplets have been formed experimentally.

• It is also considered reasonably safe to remove a single cell at this stage for diagnosis. The cell can be used to detect if the embryo is carrying a gene for a serious genetic disease such as adrenoleukodystrophy or Huntington’s disease. This is still an experimental technique rather than a routine procedure.

• The cells at the eight cell stage undergo a significant change called compaction . This involves not only a closer packing of the cells but also the production of new membrane proteins of the cadherin group which keep the cells linked together.

• The sixteen cell stage resembles a berry (blackberry, raspberry or mulberry) and is termed a morula from the Latin name for mulberry. This occurs at around 3 days (72 hours) after fertilisation.

• Up to this stage all the cells divide at approximately the same time (synchronous division) but after this stage the divisions become less co-ordinated and gradually become asynchronous.

Blastocyst formation• The next major feature is the development of a hollow cavity called the

blastocoel and this signals a significant change in the cells forming the embryo.

• A layer of cells around the blastocoel is called the trophoblast ( or trophectoderm)and this layer will be involved in the implantation of the blastocyst into the uterus but play no part in the structure of the embryo. The whole of the embryo proper comes from the inner cell mass.

• It is possible to experimentally introduce cells from a different embryo into the blastocoel and they will mix with cells already present and will help form all parts of the final embryo showing that at this stage the cells are all equivalent (multipotent) rather than being dedicated to forming one particular structure.

• An animal which has a mixture of different cells like this is termed a chimera after a mythical Greek monster which had the head of a lion, the tail of a serpent and the body of a goat).

Implantation

• It is at around this blastocyst stage ( 7-10 days) that implantation occurs.

• The zona pellucida is lost and the trophoblast cells can contact directly with the uterine lining and the blastocyst secretes enzymes which break down the lining allowing the trophoblast to penetrate into the uterine lining .

• The blastocyst is surrounded by maternal blood from eroded vessels and the trophoblast layer thickens and produces finger shaped processes (villi) and this region will later develop into the placenta.

Formation of Extra-embryonic sacs and mesoderm

• The trophoblast continues to spread and will become the chorion with extensive villi.

• Whilst implantation is occurring the inner cell mass reorganises to form a cavity called the amniotic cavity lined by epiblast cells.

• The amnion enlarges during development and completely surrounds the embryo as a fluid filled amniotic cavity which acts as a major mechanical buffer for the embryo and foetus.

• This leaves a flat disc of cells from which the embryo will form.

• The lower layer of the cell in this disc forms the hypoblast and this proliferates and migrates to form a layer surrounding a cavity referred to as the yolk sac

• This name arises by analogy with the yolk sac in other animals but in mammals this cavity never contains yolk.

• The yolk sac is an extra-embryonic structure but does act as the main source of blood cells for the early embryo though this later transfers into the main embryo.

• The epiblast forms the ectoderm of the embryo from which the epidermis and the nervous system arise while the hypoblast forms the endoderm from which the lining of the intestinal canal and its

derivative structures.

• The spaces between the amniotic cavity and the trophoblast and the yolk sac and the trophoblast become filled with cells which are believed to migrate from the epiblast layer. This middle layer is called the extra-embryonic mesoderm.

• The embryonic mesoderm develops from the endoderm by folding inwards and downwards of a furrow in the ectoderm ( this is equivalent to gastrulation in the frog where the infolding also forms the intestine and the furrow in the ectoderm is the equivalent of an extended blastopore).

• The mesoderm later forms all the muscles and connective tissues in the body.

• One final membrane develops from the endoderm of the early gut and this is the allantois.

• In birds this remains as a sac into which the waste products (eg uric acid) and presses against the shell where the lining acts as a respiratory organ for the developing chick.

• The allantois in mammals becomes part of the umbilical cord linking the embryo to the placenta.